Proton T2 relaxation time of J-coupled cerebral metabolites in rat brain at 9.4 T

Knowledge of proton T2 relaxation time of metabolites is essential for proper quantitation of metabolite concentrations in localized proton spectroscopy, especially at moderate to long TEs. Although the T2 relaxation time of singlets, such as that of creatine and N-acetylaspartate, has been characterized in several studies, similar information is lacking from coupled spin resonances of cerebral metabolites. In this study, the T2 relaxation time of coupled spin resonances and singlet resonances of cerebral metabolites was measured in rat brain in vivo at 9.4 T. Spectra were acquired at 11 TEs using the SPin ECho, full Intensity Acquired Localized (SPECIAL) spectroscopy method. Data analysis was performed in the frequency domain with the LCModel software using simulated TE-specific basis sets. The T2 relaxation times in compounds showing singlet resonances were 113 +/- 3 ms (total creatine), 178 +/- 29 ms (total choline) and 202 +/- 12 ms (N-acetylaspartate). The T2 values of J-coupled metabolites ranged from 89 +/- 8 ms (glutamate) to 148 +/- 14 ms (myo-inositol).     

Measurement of glycine in healthy and tumorous brain by triple‐refocusing MRS at 3 T in vivo

Glycine (Gly) has been implicated in several neurological disorders, including malignant brain tumors. The precise measurement of Gly is challenging largely as a result of the spectral overlap with myo‐inositol (mI). We report a new triple‐refocusing sequence for the reliable co‐detection of Gly and mI at 3 T and for the evaluation of Gly in healthy and tumorous brain. The sequence parameters were optimized with density‐matrix simulations and phantom validation. With a total TE of 134 ms, the sequence gave complete suppression of the mI signal between 3.5 and 3.6 ppm and, consequently, well‐defined Gly (3.55 ppm) and mI (3.64 ppm) peaks. In vivo ¹H magnetic resonance spectroscopy (MRS) data were acquired from the gray matter (GM)‐dominant medial occipital and white matter (WM)‐dominant left parietal regions in six healthy subjects, and analyzed with LCModel using in‐house‐calculated basis spectra. Tissue segmentation was performed to obtain the GM and WM contents within the MRS voxels. Metabolites were quantified with reference to GM‐rich medial occipital total creatine at 8 mM. The Gly and mI concentrations were estimated to be 0.63 ± 0.05 and 8.6 ± 0.6 mM for the medial occipital and 0.34 ± 0.05 and 5.3 ± 0.8 mM for the left parietal regions, respectively. From linear regression of the metabolite estimates versus fractional GM content, the concentration ratios between pure GM and pure WM were estimated to be 2.6 and 2.1 for Gly and mI, respectively. Clinical application of the optimized sequence was performed in four subjects with brain tumor. The Gly levels in tumors were higher than those of healthy brain. Gly elevation was more extensive in a post‐contrast enhancing region than in a non‐enhancing region. The data indicate that the optimized triple‐refocusing sequence may provide reliable co‐detection of Gly and mI, and alterations of Gly in brain tumors can be precisely evaluated.     

Measurement of regional variation of GABA in the human brain by optimized point‐resolved spectroscopy at 7 T in vivo

The ¹H resonances of γ‐aminobutyric acid (GABA) in the human brain in vivo are extensively overlapped with the neighboring abundant resonances of other metabolites and remain indiscernible in short‐TE MRS at 7 T. Here we report that the GABA resonance at 2.28 ppm can be fully resolved by means of echo time optimization of a point‐resolved spectroscopy (PRESS) scheme. Following numerical simulations and phantom validation, the subecho times of PRESS were optimized at (TE, TE₂) = (31, 61) ms for detection of GABA, glutamate (Glu), glutamine (Gln), and glutathione (GSH). The in vivo feasibility of the method was tested in several brain regions in nine healthy subjects. Spectra were acquired from the medial prefrontal, left frontal, medial occipital, and left occipital brain and analyzed with LCModel. Following the gray and white matter (GM and WM) segmentation of T₁‐weighted images, linear regression of metabolite estimates was performed against the fractional GM contents. The GABA concentration was estimated to be about seven times higher in GM than in WM. GABA was overall higher in frontal than in occipital brain. Glu was about twice as high in GM as in WM in both frontal and occipital brain. Gln was significantly different between frontal GM and WM while being similar between occipital GM and WM. GSH did not show significant dependence on tissue content. The signals from N‐acetylaspartylglutamate were clearly resolved, giving the concentration more than 10 times higher in WM than in GM. Our data indicate that the PRESS TE = 92 ms method provides an effective means for measuring GABA and several challenging J‐coupled spin metabolites in human brain at 7 T. Copyright © 2014 John Wiley & Sons, Ltd.     

Proton T2 relaxation of cerebral metabolites of normal human brain over large TE range

T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner. Simulations were conducted to assess the precision of T2 estimates from decay curves comprising varying numbers and ranges of TE points. Mean and standard errors for T2s of NAA, creatine and choline-containing compounds were 300(8), 169(3) and 239(4) ms in posterior frontal white matter and 256(6), 159(8) and 249(8) ms in occipital grey matter. In vivo T2s found for choline and NAA were shorter than the T2s in the literature. The elevation of literature T2s is accounted for by the simulation results, which demonstrated that there is a bias towards lengthened T2s when T2 is measured with a maximum TE approximately T2. Concentration estimates are at risk of being underestimated if previously reported T2 corrections are used.     

The age dependence of T2 relaxation times of N‐acetyl aspartate,creatine and choline in the human brain at 3 and 4T

Knowledge of the T₂ age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T₂ values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T₂ values of N‐acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (T_E = 30–540 ms, 9 young and 11 elderly subjects) and 4T (T_E = 10–180 ms, 18 young and 14 elderly subjects) using single‐voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion‐recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different T_E range. Individual estimated T₂ values were statistically analyzed using the R programming language for the age dependence of T₂ values as well as the influence of the MM baseline handling. A significant decrease of T₂ values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T₂ values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T₂ values, we confirmed the age dependence of T₂ values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.     

White matter microstructure and longitudinal relaxation time anisotropy in human brain at 3 and 7 T

A high degree of structural order by white matter (WM) fibre tracts creates a physicochemical environment where water relaxations are rendered anisotropic. Recently, angularly dependent longitudinal relaxation has been reported in human WM. We have characterised interrelationships between T1 relaxation and diffusion MRI microstructural indices at 3 and 7 T. Eleven volunteers consented to participate in the study. Multishell diffusion MR images were acquired with b-values of 0/1500/3000 and 0/1000/2000 s/mm² at 1.5 and 1.05 mm³ isotropic resolutions at 3 and 7 T, respectively. DTIFIT was used to compute DTI indices; the fibre-to-field angle (θ_FB) maps were obtained using the principal eigenvector images. The orientations and volume fractions of multiple fibre populations were estimated using BedpostX in FSL, and the orientation dispersion index (ODI) was estimated using the NODDI protocol. MP2RAGE was used to acquire images for T1 maps at 1.0 and 0.9 mm³ isotropic resolutions at 3 and 7 T, respectively. At 3 T, T1 as a function of θ_FB in WM with high fractional anisotropy and one-fibre orientation volume fraction or low ODI shows a broad peak centred at 50^o, but a flat baseline at 0^o and 90^o. The broad peak amounted up to 7% of the mean T1. At 7 T, the broad peak appeared at 40^o and T1 in fibres running parallel to B0 was longer by up to 75 ms (8.3% of the mean T1) than in those perpendicular to the field. The peak at 40^o was approximately 5% of mean T1 (i.e., proportionally smaller than that at 54^o at 3 T). The data demonstrate T1 anisotropy in WM with high microstructural order at both fields. The angular patterns are indicative of the B0-dependency of T1 anisotropy. Thus myelinated WM fibres influence T1 contrast both by acting as a T1 contrast agent and rendering T1 dependent on fibre orientation with B0.     

The in vivo influence of white matter fiber orientation towards B0 on T2* in the human brain

It is well known that, at higher field strength, T2*‐weighted images show an extensive heterogeneity in white matter fiber bundles. The basis of this phenomenon is still under discussion, as many factors, such as iron concentration, myelination and tissue microstructure, could influence relaxation times. Furthermore, fiber direction in relation to the main magnetic field seems to influence T2* relaxation times. In this study, diffusion tensor imaging and T2* measurements were combined in seven subjects with the head in a normal and tilted position. It was shown that fiber orientation has a strong influence on T2* in the human brain, with the average T2* value changing from 49 ms for a perpendicular orientation to B₀ to 57 ms for a parallel orientation to B₀. Nevertheless, T2* times showed a wide variety of values at any orientation towards B₀. Copyright © 2010 John Wiley & Sons, Ltd.     

Simultaneous observation of glutamate, gamma-aminobutyric acid, and glutamine in human brain at 4.7 T using localized two-dimensional constant-time correlation spectroscopy

Localized two-dimensional constant-time correlation spectroscopy (CT-COSY) was used to resolve glutamate (Glu), gamma-aminobutyric acid (GABA), and glutamine (Gln) in the human brain at 4.7 T. In this method, three-dimensional localization was achieved using three radio frequency pulses of the CT-COSY module for slice selection. As this sequence could decouple JHH along the F1 direction, peak resolution of metabolites was improved even on a magnitude-mode display. In experiments on a phantom containing N-acetylaspartate, creatine, Glu, Gln, and GABA with a constant time delay (Tct) of 110 ms, cross peaks of Glu, Gln, and GABA were obtained on a spectrum processed with standard sine-bell windows, which emphasize sine-dependent signals along the t2 direction. In contrast, diagonal peaks of Glu C4H at 2.35 ppm, GABA C2H at 2.28 ppm, and Gln C4H at 2.44 ppm were resolved on a spectrum processed with Gaussian windows, which emphasize cosine-dependent signals along t2. Human brain spectra were obtained from a 27 mL voxel within the parieto-occipital region using a volume transverse electromagnetic (TEM) coil for both transmission and reception. Tct was 110 ms; the total scan time was 30 min. Diagonal peaks of Glu C4H, GABA C2H, and Gln C4H were also resolved on the spectrum processed with Gaussian windows. These results show that the localized two-dimensional CT-COSY method featuring 1H decoupling along the F1 direction could resolve Glu, GABA, and Gln signals in the human brain.     

Proton T1 relaxation times of cerebral metabolites differ within and between regions of normal human brain

Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in occipital grey, parietal white and frontal white matter (10 subjects each location). Spectra were also acquired at 7, 21 and 37 degrees C from separate 100 mm solutions of inositol (Ins), choline-containing compounds (Cho), N-acetyl-aspartate (NAA) and creatine. Simulations of T(1) fits with 2, 3 and 7 TRs demonstrated that at typical SNR there is potential for both inaccurate and biased results. In vivo, different metabolites had significantly different T(1)s within the same brain volume. The same order from shortest to longest T(1) (Ins, Cho, NAA, creatine) was found for all three brain regions. The order (Ins, NAA, creatine, Cho) was found in the metabolite solutions and was consistent with a simple model in which T(1) is inversely proportional to molecular weight. For all individual metabolites, T(1) increased from occipital grey to parietal white to frontal white matter. This study demonstrates that, in spectra acquired with TR near 1 s, T(1) weightings are substantially different for metabolites within a single tissue and also for the same metabolites in different tissues.     

Rapid multi‐echo measurement of brain metabolite T2 values at 7 T using a single‐shot spectroscopic Carr–Purcell–Meiboom–Gill sequence and prior information

We present a method for the robust and accurate estimation of brain metabolite transverse relaxation times (T₂) from multiple spin‐echo data acquired with a single‐shot Carr–Purcell–Meiboom–Gill (CPMG) spectroscopic sequence. Each acquired echo consists of a small number of complex time‐domain data points. The amplitudes of the spectral components in each echo are calculated by solving a set of linear equations in which previously estimated frequencies and linewidths serve as prior information. These priors are obtained from a short MRS experiment in which a large number of time‐domain data points are acquired, and are subsequently estimated using linear prediction with singular value decomposition (LPSVD) processing. We show that this process can be used to accurately and rapidly measure the T₂ values for the main singlet resonances in single‐volume MRS measurements in the brain. The proposed method can be generalized to any set of MRS experiments comprising repeated measurements of amplitude changes, e.g. as a function of an experimental parameter, such as TE, inversion time or diffusion weighting. Copyright © 2013 John Wiley & Sons, Ltd.     

Inversion recovery ultrashort echo time imaging of ultrashort T2 tissue components in ovine brain at 3 T: a sequential D2O exchange study

Inversion recovery ultrashort echo time (IR‐UTE) imaging holds the potential to directly characterize MR signals from ultrashort T₂ tissue components (STCs), such as collagen in cartilage and myelin in brain. The application of IR‐UTE for myelin imaging has been challenging because of the high water content in brain and the possibility that the ultrashort T₂* signals are contaminated by water protons, including those associated with myelin sheaths. This study investigated such a possibility in an ovine brain D₂O exchange model and explored the potential of IR‐UTE imaging for the quantification of ultrashort T₂* signals in both white and gray matter at 3 T. Six specimens were examined before and after sequential immersion in 99.9% D₂O. Long T₂ MR signals were measured using a clinical proton density‐weighted fast spin echo (PD‐FSE) sequence. IR‐UTE images were first acquired with different inversion times to determine the optimal inversion time to null the long T₂ signals (TI_null). Then, at this TI_null, images with echo times (TEs) of 0.01–4 ms were acquired to measure the T₂* values of STCs. The PD‐FSE signal dropped to near zero after 24 h of immersion in D₂O. A wide range of TI_null values were used at different time points (240–330 ms for white matter and 320–350 ms for gray matter at TR = 1000 ms) because the T₁ values of the long T₂ tissue components changed significantly. The T₂* values of STCs were 200–300 μs in both white and gray matter (comparable with the values obtained from myelin powder and its mixture with D₂O or H₂O), and showed minimal changes after sequential immersion. The ultrashort T₂* signals seen on IR‐UTE images are unlikely to be from water protons as they are exchangeable with deuterons in D₂O. The source is more likely to be myelin itself in white matter, and might also be associated with other membranous structures in gray matter.     

A comparative study of short‐ and long‐TE 1H MRS at 3 T for in vivo detection of 2‐hydroxyglutarate in brain tumors

2‐Hydroxyglutarate (2HG) is produced in gliomas with mutations of isocitrate dehydrogenase (IDH) 1 and 2. The ¹H resonances of the J‐coupled spins of 2HG are extensively overlapped with signals from other metabolites. Here, we report a comparative study at 3 T of the utility of the point‐resolved spectroscopy sequence with a standard short TE (35 ms) and a long TE (97 ms), which had been theoretically designed for the detection of the 2HG 2.25‐ppm resonance. The performance of the methods is evaluated using data from phantoms, seven healthy volunteers and 22 subjects with IDH‐mutated gliomas. The results indicate that TE = 97 ms provides higher detectability of 2HG than TE = 35 ms, and that this improved capability is gained when data are analyzed with basis spectra that include the effects of the volume localizing radiofrequency and gradient pulses. Copyright © 2013 John Wiley & Sons, Ltd.     

Improvement of resolution for brain coupled metabolites by optimized (1)H MRS at 7T

Resolution enhancement for glutamate (Glu), glutamine (Gln) and glutathione (GSH) in the human brain by TE‐optimized point‐resolved spectroscopy (PRESS) at 7 T is reported. Sub‐TE dependences of the multiplets of Glu, Gln, GSH, γ‐aminobutyric acid (GABA) and N‐acetylaspartate (NAA) at 2.2–2.6 ppm were investigated with density matrix simulations, incorporating three‐dimensional volume localization. The numerical simulations indicated that the C4‐proton multiplets can be completely separated with (TE₁, TE₂) = (37, 63) ms, as a result of a narrowing of the multiplets and suppression of the NAA 2.5 ppm signal. Phantom experiments reproduced the signal yield and lineshape from simulations within experimental errors. In vivo tests of optimized PRESS were conducted on the prefrontal cortex of six healthy volunteers. In spectral fitting by LCModel, Cramér–Rao lower bounds (CRLBs) of Glu, Gln and GSH were 2 ± 1, 5 ± 1 and 6 ± 2 (mean ± SD), respectively. To evaluate the performance of the optimized PRESS method under identical experimental conditions, stimulated‐echo spectra were acquired with (TE, TM) = (14, 37) and (74, 68) ms. The CRLB of Glu was similar between PRESS and short‐TE stimulated‐echo acquisition mode (STEAM), but the CRLBs of Gln and GSH were lower in PRESS than in both STEAM acquisitions. Copyright © 2010 John Wiley & Sons, Ltd.     

Measuring renal tissue relaxation times at 7 T

As developments in RF coils and RF management strategies make performing ultra‐high‐field renal imaging feasible, understanding the relaxation times of the tissue becomes increasingly important for tissue characterization, sequence optimization and quantitative functional renal imaging, such as renal perfusion imaging using arterial spin labeling. By using a magnetization‐prepared single‐breath‐hold fast spin echo imaging method, human renal T₁ and T₂ imaging studies were successfully performed at 7 T with 11 healthy volunteers (eight males, 45 ± 17 years, and three females, 29 ± 7 years, mean ± standard deviation, S.D.) while addressing challenges of B₁⁺ inhomogeneity and short‐term specific absorption rate limits. At 7 T, measured renal T₁ values for the renal cortex and medulla (mean ± S.D.) from five healthy volunteers who participated in both 3 T and two‐session 7 T studies were 1661 ± 68 ms and 2094 ± 67 ms, and T₂ values were 108 ± 7 ms and 126 ± 6 ms. For comparison, similar measurements were made at 3 T, where renal cortex and medulla T₁ values of 1261 ± 86 ms and 1676 ± 94 ms and T₂ values of 121 ± 5 ms and 138 ± 7 ms were obtained. Measurements at 3 T and 7 T were significantly different for both T₁ and T₂ values in both renal tissues. Reproducibility studies at 7 T demonstrated that T₁ and T₂ estimations were robust, with group mean percentage differences of less than 4%. Copyright © 2014 John Wiley & Sons, Ltd.     

A rapid inversion technique for the measurement of longitudinal relaxation times of brain metabolites: application to lactate in high‐grade gliomas at 3 T

The aim of this study was to develop a time‐efficient inversion technique to measure the T₁ relaxation time of the methyl group of lactate (Lac) in the presence of contaminating lipids and to measure T₁ at 3 T in a cohort of primary high‐grade gliomas. Three numerically optimized inversion times (TIs) were chosen to minimize the expected error in T₁ estimates for a given input total scan duration (set to be 30 min). A two‐cycle spectral editing scheme was used to suppress contaminating lipids. The T₁ values were then estimated from least‐squares fitting of signal measurements versus TI. Lac T₁ was estimated as 2000 ± 280 ms. After correcting for T₁ (and T₂ from literature values), the mean absolute Lac concentration was estimated as 4.3 ± 2.6 mm . The technique developed agrees with the results obtained by standard inversion recovery and can be used to provide rapid T₁ estimates of other spectral components as required. Lac T₁ exhibits similar variations to other major metabolites observable by MRS in high‐grade gliomas. The T₁ estimate provided here will be useful for future MRS studies wishing to report relaxation‐corrected estimates of Lac concentration as an objective tumor biomarker. Copyright © 2016 John Wiley & Sons, Ltd.     

In vivo T2 relaxation time measurement with echo‐time averaging

The accuracy of metabolite concentrations measured using in vivo proton (¹H) MRS is enhanced following correction for spin–spin (T₂) relaxation effects. In addition, metabolite proton T₂ relaxation times provide unique information regarding cellular environment and molecular mobility. Echo‐time (TE) averaging ¹H MRS involves the collection and averaging of multiple TE steps, which greatly simplifies resulting spectra due to the attenuation of spin‐coupled and macromolecule resonances. Given the simplified spectral appearance and inherent metabolite T₂ relaxation information, the aim of the present proof‐of‐concept study was to develop a novel data processing scheme to estimate metabolite T₂ relaxation times from TE‐averaged ¹H MRS data. Spectral simulations are used to validate the proposed TE‐averaging methods for estimating methyl proton T₂ relaxation times for N‐acetyl aspartate, total creatine, and choline‐containing compounds. The utility of the technique and its reproducibility are demonstrated using data obtained in vivo from the posterior‐occipital cortex of 10 healthy control subjects. Compared with standard methods, distinct advantages of this approach include built‐in macromolecule resonance attenuation, in vivo T₂ estimates closer to reported values when maximum TE ≈ T₂, and the potential for T₂ calculation of metabolite resonances otherwise inseparable in standard ¹H MRS spectra recorded in vivo. Copyright © 2014 John Wiley & Sons, Ltd.     

Noninvasive quantification of T2 and concentrations of ascorbate and glutathione in the human brain from the same double-edited spectra

The transverse relaxation times (T₂) and concentrations of Ascorbate (Asc) and glutathione (GSH) were measured from a single dataset of double‐edited spectra that were acquired at several TEs at 4 T in the human brain. Six TEs between 102 and 152 ms were utilized to calculate T₂ for the group of 12 subjects scanned five times each. Spectra measured at all six TEs were summed to quantify the concentration in each individual scan. LCModel fitting was optimized for the quantification of the Asc and GSH double‐edited spectra. When the fitted baseline was constrained to be flat, T₂ was found to be 67 ms (95% confidence interval, 50–83 ms) for GSH and ≤115 ms for Asc using the sum of spectra measured over 60 scans. The Asc and GSH concentrations quantified in each of the 60 scans were 0.62 ± 0.08 and 0.81 ± 0.11 µmol/g [mean ± standard deviation (SD), n = 60], respectively, using 10 µmol/g N‐acetylaspartate as an internal reference and assuming a constant influence of N‐acetylaspartate and antioxidant T₂ relaxation in the reference solution and in vivo. The T₂ value of GSH was measured for the first time in the human brain. The data are consistent with short T₂ for both antioxidants. These T₂ values are essential for the absolute quantification of Asc and GSH concentrations measured at long TE, and provide a critical step towards addressing assumptions about T₂, and therefore towards the quantification of concentrations without the possibility of systematic bias. Copyright © 2010 John Wiley & Sons, Ltd.     

Doubly selective multiple quantum chemical shift imaging and T1 relaxation time measurement of glutathione (GSH) in the human brain in vivo

Mapping of a major antioxidant, glutathione (GSH), was achieved in the human brain in vivo using a doubly‐selective multiple quantum filtering based chemical shift imaging (CSI) of GSH at 3 T. Both in vivo and phantom tests in CSI and single voxel measurements were consistent with excellent suppression of overlapping signals from creatine, γ‐Amino butyric acid (GABA) and macromolecules. GSH concentration in the fronto‐parietal region was 1.20 ± 0.16 µmol/g (mean ± SD, n = 7). The longitudinal relaxation time (T₁) of GSH in the human brain was 397 ± 44 ms (mean ± SD, n = 5), which was substantially shorter than that of other metabolites. This GSH‐CSI method permits us to address regional differences of GSH in the human brain under conditions where oxidative stress has been implicated, including multiple sclerosis, aging and neurodegenerative diseases. Copyright © 2012 John Wiley & Sons, Ltd.     

In vivo 31P MRS assessment of intracellular NAD metabolites and NAD+/NADH redox state in human brain at 4 T

NAD⁺ and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD⁺/NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo ³¹P MRS‐based NAD assay for noninvasive and quantitative measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T. To explore its potential for clinical application, in this study we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a lower field of 4 T by incorporating the ¹H‐decoupling technique with the in vivo ³¹P NAD assay. The use of ¹H decoupling significantly narrowed the linewidths of NAD and α‐ATP resonances, resulting in higher sensitivity and better spectral resolution as compared with the ¹H‐coupled ³¹P spectrum. These improvements made it possible to reliably quantify cerebral NAD concentrations and RX, consistent with previously reported results obtained from similar age human subjects at 7 T. In summary, this work demonstrates the capability and utility of the ¹H‐decoupled ³¹P MRS‐based NAD assay at lower field strength; thus, it opens new opportunities for studying intracellular NAD metabolism and redox state in human brain at clinical settings. This conclusion is supported by the simulation results, indicating that similar performance and reliability as observed at 4T can be achieved at 3 T with the same signal‐to‐noise ratio. Copyright © 2016 John Wiley & Sons, Ltd.     

Short-TE localised 1H MRS of the human brain at 3 T: quantification of the metabolite signals using two approaches to account for macromolecular signal contributions

The goal of this study was to validate metabolite quantification at short TE, with particular focus on how to best account for the macromolecular signal contribution. A robust, short-TE PRESS protocol is presented, which allows reliable quantification, in vivo, of metabolite signals at 3 T in human brain. Water suppression was adapted to the experimental conditions at 3 T. Metabolite signal from the parietal white matter was quantified in the time domain using QUEST (jMRUI). The increased macromolecular signal contribution at short TE was dealt with by two approaches, based on either metabolite nulling or initial signal truncation. A detailed comparison of the two approaches was made. The first used a metabolite-nulled signal, measured either individually or averaged over different subjects. The second used the total signal, metabolites and macromolecules, from a single scan. The two approaches gave similar quantification results in terms of metabolite concentrations, but differed in their precision and the number of metabolites quantified reliably. With an average metabolite-nulled baseline, a set of seven metabolites could be reliably quantified in parietal white matter under these experimental conditions: N-acetylaspartate, myo-inositol, glucose, glutamate, glutathione, creatine and choline. When initial signal truncation was used, glucose was removed from this set. The short TE (10-11 ms) facilitated quantification of glutamate. The reliable quantification of N-acetylaspartyl glutamate at 3 T proved very difficult.